Method and apparatus to measure blood flow and recirculation in hemodialysis shunts

ABSTRACT

The measurement of blood flow in a dialysis shunt is obtained by injection of an indicator material into a venous line leading from dialysis equipment to the shunt. The blood flow in an arterial line leading from the shunt at a location downstream of the venous line to the dialysis equipment is monitored by an arterial line sensor for the presence of the indicator material. A detector connected to the sensor provides a dilution curve in response to the presence of the indicator material and the blood flow in the shunt is calculated from the area under the dilution curve. The locations of the arterial and venous lines in the shunt can be reversed to obtain a measurement of blood recirculation from the venous line into the arterial line.

BACKGROUND OF THE INVENTION

[0001] The invention relates to the field of kidney dialysis processesand more particularly to such processes for measuring arterio-venousshunt blood flow and undesirable recirculation during hemodialysis.

[0002] Dialysis is a process by which an artificial kidney replaces thefunction of a patient's kidney. Blood is removed from the patient'svascular system via an arterial line, is passed through a dialyzer andis returned to the patient via a venous line for normal circulationthrough the patient's vascular system. A majority of dialysis patientshave an arterio-venous shunt implanted in a location having a high bloodflow that simplifies the withdrawal of blood from the part that iscloser to the arterial side of the shunt and the return of purifiedblood downstream of the withdrawal site, closer to venous side of theshunt. In some cases the shunt clots or stenoses and the resultingreduction in blood flow necessitates surgery that is costly and invasivefor the patient. In the situation of low blood flow in the shunt or, ifthere is any other problem with the venous outflow, some part of thefreshly dialyzed blood from the venous return line flows directly to thearterial withdrawal line where it is again filtered. If this undesireddirect recirculation level is high enough, some amount of blood will berepeatedly refiltered and the rest of the patient's blood will not besufficiently filtered to provide the patient with adequate dialysis.

[0003] One method of measuring shunt blood flow currently uses colorcoded duplex sonography. This is very expensive and involves operationby highly-qualified professionals. Measurements are therefore made onlyrarely and the onset of reduced flow, when treatment could be madewithout surgery can be missed.

[0004] The standard test for undesired direct recirculation requiresthree blood samples while the patient is on dialysis. This methodrequires blood samples from the patient, time from the nurses, and highlaboratory costs. Dialysis patients generally have lower hematocrit thanthe normal population and are at greater risk from losing blood, so thisis not very satisfactory.

[0005] Another technique involves injection of a saline solutionintravenously and recording changes of blood optical properties fordetecting recirculation qualitatively. This technique leaves open thequestion of whether recirculation is quantitatively reduced sufficientlyto warrant intervention.

SUMMARY OF THE INVENTION

[0006] The present invention avoids the problems encountered withprevious methods and techniques by providing an accurate determinationof shunt blood flow and undesired recirculation at lower cost.

[0007] Blood flow, Q, measured by the dilution method (A. C. GuytonTextbook of Medical Physiology, Sixth Edition, p. 287, 1981) is givenby: Q=V/S (Eq 1) where V is the amount of injected indicator and S isthe area under a dilution curve and is equal to the averageconcentration of indicator in the blood for the duration of the curve,multiplied by the duration of the curve.

[0008] A dilution curve is obtained by measuring changes in a physicalparameter of the blood over a period of time, and plotting the resultingvariations. For example, if the blood parameter being measured is soundvelocity, the injection of an indicator such as a saline solution,having a different sound velocity than blood, will produce a change inthe measured parameter as the indicator passes the sensor location. Theindicator dilutes the blood, and produces a sound velocity curve whichis a measure of that dilution. Although injection of a saline solutionis convenient for producing a measurable change in a blood parametersuch as sound velocity, other changes of parameters may also besuitable. Thus, changes in temperature, electrical impedance, opticalcharacteristics, and the like may also be used as indicators to producedilution curves. For purposes of this disclosure, however, referencewill primarily be made to the use of saline solution as the indicator,with resulting changes in sound velocity in the blood being measured toprovide a dilution curve.

[0009] To facilitate the measurement of shunt blood flow in accordancewith the present invention, the blood line connection is reversed fromnormal; that is, the arterial inlet which removes the blood from thepatient for dialysis is located downstream (not upstream as normal) ofthe venous outlet in the shunt. A volume of indicator, such as a salinesolution, is injected into the venous line (V_(ven)), where it is mixedwith the dialyzer blood flow Q_(dial) and the mixture is delivered tothe shunt where it is combined with the blood flow in the shunt(Q_(shunt)) The blood shunt flow (Q_(shunt)) can be calculated fromEquation 1 by measuring the dilution area in the arterial line S_(art):

Q _(shunt) +Q _(dial) =V _(ven) /S _(art)   (Eq 2)

[0010] or

Q _(shunt) =V _(ven) /S _(art) −Q _(dial)   (Eq. 3)

[0011] Equation 3 shows that if the blood flow through the dialyzerQ_(dial) is measured and the absolute concentration of indicator in thearterial blood line S_(art) is recorded, then the blood flow through theshunt Q_(shunt) can be calculated.

[0012] In some methods applicable to hemodialysis, sensors are clampedonto the exterior of the arterial or venous line, or tube. However, itis difficult to measure the absolute concentration of indicator in theblood through the hemodialysis tube. For example, if a sound velocitysensor is used to record protein concentration changes in blood due to asaline indicator injection, the sound beam will have to pass throughboth the tube and the blood. Recorded measurements of absolute soundvelocity will be influenced not only by the blood, but also by theunknown sound properties of the tube. The same problem occurs if anoptical sensor is clamped onto tube; i.e., the recorded amplitude of alight beam is not only the function of hemoglobin concentration but oftube properties.

[0013] This problem may be solved by an additional calibration injectionof the same indicator, which is injected in the arterial line, butupstream of the place where the measurements are made. The equation forthis case will be: Q_(dial)=V_(cal)/S_(cal) (Eq 4) where V_(cal) is theknown quantity of indicator in the calibration injection and S_(cal) isthe area under the resulting dilution curve. This area is the averageconcentration of indicator in the blood for the duration of the curve,times the duration of the curve.

[0014] From Equations 2 and 4 the formula for shunt blood flow will be:

Qshunt=Q _(dial)(V _(ven) /V _(cal) *S _(cal) /S _(art)−1)   (Eq. 5)

[0015] or

Q _(shunt)=(V _(ven) /S _(art) −V _(cal) /S _(cal))   (Eq. 6)

[0016] Equation 5 is suitable if blood flow in the tube can be measuredaccurately. The ratio S_(cal)/S_(art) shows that the recorded dilutionareas only need to be proportional to relative changes in concentrationsin this case. Assuming that tube properties are constant during themeasurements, the value of this ratio can be calculated with highaccuracy for most type of sensors, including sound velocity, optical,etc.

[0017] Equation 6 can be used where tube blood flow is unknown butabsolute concentrations are measured, for instance by withdrawing theblood from the arterial blood line and using an optical densitometer foroptical dye dilution measurements.

[0018] To avoid the need for a calibration injection, an additionalsensor that is matched to the arterial line sensor is located on thevenous line downstream of the location of the intravenous indicatorinjection. For this case, the injected indicator will be mixed with thevenous line tube flow, so by analogy with the calibration injection ofEquation 4: Q _(dia)1=V _(ven) /S _(ven)  (Eq. 7)

[0019] where S_(ven) is the area under the dilution curve and iscalculated as the average concentration of indicator in the blood forthe duration of curve, times the duration of the curve. From the sameinjection, the area S_(art) is generated. The formula for blood flow bysubstituting in Equation 5 is:

Q _(shunt) =Q _(dia)1(S _(ven) /S _(art)−1)   (eq. 8).

[0020] As an alternative to the foregoing, a measurement of the quantityof blood recirculation may be made during a normal connection of thedialysis blood lines of the shunt, with the intake to the arterial linebeing upstream in the shunt and the outlet of the venous line connectionbeing downstream in the shunt. With this “normal” connection, afterinjecting an indicator into the venous line, a rapid appearance ofindicator in the arterial line is an indication that recirculationexists. The quantity of recirculation is the fraction of freshlyfiltered blood in the venous line that recirculates to the arterial lineand this quantity is equal to the ratio of indicator volume that isrecirculated into the arterial line (V_(rec)) to the volume that wasinjected into the venous line (V_(ven)).

[0021] The amount of recirculated indicator V_(rec) is equal to the areaunder the recirculated concentration dilution curve S_(rec) multipliedby the dialysis blood flow in the arterial line Q_(dial):

V _(rec) =S _(rec) *Q _(dial)   (Eq. 9)

[0022] The same problem with the evaluation of Srec that was describedfor Equations 2 and 3 persists; namely, the difficulty of measuringindicator concentration through the tubing. This problem is avoided byan additional calibration injection of the same indicator into thearterial line upstream from the place where the measurements are made,as discussed above with respect to Equation 4. From Equations 4 and 9the recirculating fraction is:

V _(rec) /V _(ven) =V _(cal) /V _(ven) *S _(rec) /S _(cal)   (eq. 10)

[0023] The ratio S_(rec)/S_(cal) in Equation 10 indicates that themeasured dilution areas need only be in the same relative units.Assuming that tube properties are constant during the measurements, thisratio can be calculated with high accuracy for most types of sensors;e.g., sound velocity, optical, etc.

[0024] To avoid the need for a calibration injection, an additionalsensor that is matched to the arterial line sensor may be located on thevenous line downstream of the location of the intravenous indicatorinjection. For this case, the injected indicator will be mixed with thevenous line flow, so by analogy with the calibration injection Equation7:

V _(rec) /V _(ven) =S _(rec) /S _(ven)   (Eq. 11)

[0025] In summary, the, shunt blood flow can be measured by reversingarterial and venous blood lines. An arterial inlet, which removes bloodfrom a patient's vascular system, is located in the shunt downstream ofa venous outlet, which returns treated blood to the patient's vascularsystem. An indicator material is injected into an injection port in thevenous tube, and changes in the physical properties of the blood aremonitored in the arterial line. These changes are recorded, with thearea under the resulting dilution curve providing a measure of bloodflow in the shunt and tube line. The indicator used for this purpose isany material or blood treatment which changes the physicalcharacteristics of the blood. For example, it can be a saline solution,preferably of known concentration, or can be a heating or cooling of aquantity of blood. The change of characteristics is measured by knownsensors, such as sound velocity sensors, electrical impedance sensors,optical sensors, thermal sensors, isotope sensors, or the like, and theblood flow relationships are calculated in accordance with the foregoingequations.

[0026] Because the tubing used to carry blood from the patient to thedialysis equipment introduces errors into the measurements of bloodflow, calibration measurements may be required, using a calibrationinjection and, if blood flow is unknown, blood concentrationmeasurements. To avoid the need for a calibration injection, anadditional sensor may be provided on the venous line downstream of thevenous injection port.

[0027] Blood recirculation can also be measured with the arterial inletlocated in the shunt upstream of the venous outlet. In this case, theindicator is injected into an injection port in the venous line outlet(as before) and the blood characteristics are monitored in the arterialline. A calibration injection may be provided at an injection port inthe arterial line upstream of the arterial tube monitor or, to avoid acalibration injection, a second blood characteristic monitor can beprovided in the venous tube downstream of the venous injection port.

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The foregoing, and additional objects, features, and advantagesof the present invention will become apparent to those of skill in theart from the following detailed description of preferred embodimentsthereof, taken in conjunction with the accompanying drawings, in which:

[0029]FIG. 1 is a diagrammatic illustration of an arterio-venous shuntconnected by way of arterial and venous tubes to a dialyzer with anarterial tube inlet in the shunt downstream from a venous tube outlet,an injection port in the venous tube, and a sensor for the arterialtube;

[0030]FIG. 1A illustrates a dilution curve for the device of FIG. 1;

[0031]FIG. 2 is a modification of FIG. 1, adding a second sensor for thearterial tube;

[0032]FIG. 3 is a second modification of FIG. 1, adding an injectionport in the arterial tube, upstream of the arterial sensor;

[0033]FIG. 3A illustrates a dilution curve for the device of FIG. 3;

[0034]FIG. 4 is a third modification of FIG. 1, adding to the device ofFIG. 3 a second arterial sensor of the type illustrated in FIG. 2;

[0035]FIG. 5 is a fourth modification of FIG. 1, incorporating twoadditional sensors, one for each of the venous and arterial tubes;

[0036]FIGS. 5A and 5B illustrate dilution curves for the device of FIG.5;

[0037]FIG. 6 is a diagrammatic illustration of a second embodiment ofthe invention, illustrating an arterio-venous shunt connected by way ofarterial and venous tubes to a dialyzer, with an arterial tube inlet inthe shunt upstream of a venous tube outlet, an injection port in thevenous tube, a sensor for the arterial tube and a calibration port inthe arterial tube upstream of the sensor; and

[0038]FIG. 7 is a diagrammatic illustration of a modification of thedevice of FIG. 6, wherein the calibration port of FIG. 6 is replaced bya venous tube sensor downstream of the venous tube injection port.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0039] Turning now to a more detailed consideration of the process ofdetermining blood flow in a dialysis shunt in accordance with thepresent invention there is illustrated in FIG. 1 a patient blooddialysis system 10 utilizing a reversed connection of arterial andvenous lines to a blood vessel 12 illustrated as an arterio-venous shuntconnected at its upstream end 14 to a patient's artery 16 and connectedat its downstream end 18 to a patient's blood vein 20. The shunt may bean artificial vessel or a native vessel that is surgically moved betweenartery 16 and vein 20. The direction of flow of blood in the vessel 12is indicated by arrow 22 and it is this blood flow which is to bedetermined. Connected between vessel 12 and conventional blood dialysisequipment 24 is an arterial line, or tube 26 having an inlet 28 in theshunt 12 for drawing blood for treatment by the dialysis equipment. Thedirection of flow of blood in arterial line 26 is illustrated by arrow30.

[0040] Also connected between the dialysis equipment 24 and shunt 12 isa venous line, or tube, 32 which carries treated blood from the dialysisequipment 24 back to the shunt. The venous line 32 has an outlet 34located in shunt 12, upstream of the arterial line inlet 28. Thedirection of flow of treated blood in venous line 32 is illustrated byarrow 36. As illustrated by arrow 38, treated blood from the outlet 34travels downstream, in the direction of the main flow 22, toward theinlet 28 where some of the treated blood 38 is collected by the arterialline 26.

[0041] Measurement of blood flow in the shunt is obtained, in accordancewith the invention, by injecting into venous line 32, as by way of aninjection port 40, an indicator material having a selected physicalproperty differing from that of the blood being treated. In thepreferred embodiment, this material, indicated by arrow 42, is a salinesolution which is isotonic with the blood but which has different soundvelocity properties. Other indicator materials may be, for example,heated or cooled blood. The injected indicator is mixed with the bloodflow 36 in the venous line and is returned to shunt 12 where it is mixedwith the shunt flow 22. A portion of the indicator is withdrawn from theshunt by the arterial blood line, as indicated by arrow 30.

[0042] A sensor 50 is provided at a location downstream of the injectionport 40, and preferably is located in the arterial line 26, asillustrated in FIG. 1. The sensor preferably is a blood sound velocitydetector which comprises a sound source 52 sending a sound beam directlythrough the blood passing through arterial line 26 to a sound receiver54 which produces an output signal related to the velocity of sound inthe blood. Such sound velocity sensors are well known in the art and areexemplified by the Transonic 4x perivascular probe manufactured byTransonic Systems, Inc., Ithaca, N.Y., U.S.A. In this probe, thereceiver 54 produces an output signal on line 56 which is directed to adetector 58 which measures and evaluates the signal supplied by way ofline 56. The detector records the signal and carries out thecalculations described above for converting the sensor output signal toa blood concentration signal for determination of the blood flow in theshunt 12 and through the dialysis equipment 24. If the blood flow in thedialysis equipment 24 is significant in comparison to the flow in shunt12, the measurements made by sensor 50 will give results which overstate the flow of the shunt.

[0043] More particularly, the blood flow Q in shunt 12 may be calculatedin accordance with Equation 1 by calculating the area under the dilutioncurve obtained by sensor 50. Art example of such a curve is illustratedin FIG. 1A, wherein the velocity of sound in the arterial blood flow isillustrated by curve 59. At time 0 an indicator material is injected atport 40, and at some later time, the change in sound velocity caused bythe indicator is detected at sensor 50, as illustrated by the dip, ordilution area, 59 a in curve 59. The area under the dilution curve 59 inregion 59 a is the area Sart described in Equation 2.

[0044] As illustrated in FIG. 2, a second blood flow sensor 60 may beprovided on arterial line 26 and connected by way of line 62 to thedetector 58. This second sensor is a blood flow sensor such as a modelHT109 clamp-on flowmeter produced by Transonic Systems, Inc., and isused to measure the blood flow Qdial in line 26 so that it can besubtracted from the sum of flows calculated in accordance with theembodiment of in FIG. 1 to increase the accuracy of the shunt blood flowdetermination. This improved accuracy is obtained in accordance withEquations 2 and 3. Although sensor 60 is shown as separate from sensor50, the two sensors may be incorporated into a single unit, if desired.

[0045] Another modification of the invention is illustrated in FIG. 3,which is the same as FIG. 1 but with the addition of an injection port70 in the arterial line 26 for injecting a calibration indicatormaterial, shown by line 72. This injection port 70 is located upstreamof the sensor 50 so that the indicator material 72 is mixed with all ofthe blood flow in line 26. The injection of the calibration indicatormaterial in port 70 produces a corresponding dilution curve illustratedat 74 in FIG. 3A in accordance with the change in sound velocity in theblood, as sensed by sensor 50, and this dilution curve is recorded bydetector 58. The detector determines the blood flow Q_(dial) in line 26from the area S_(cal) under curve 74 and from the known volume V_(cal)of indicator material 72, in accordance with equation 4. This blood flowQ_(dail) is then subtracted from the sum of flows calculated inaccordance with FIG. 1 to increase the accuracy of the shunt blood flowmeasurement, in accordance with Equation 6.

[0046] Another embodiment of the invention is illustrated in FIG. 4,which includes all of the measurements of FIGS. 1, 2, and 3. Thus, thedevice of FIG. 4 includes sensor 50 with a sound source 52 and a soundreceiver 54 supplying signals on line 56 to detector 58, includes ablood flow sensor 60 connected by way of line 62 to detector 58, andincludes a calibration injection port 70 for receiving calibrationindicator material 72. The output signal on line 62 is for measuring thedialysis blood flow Q_(dial) The indicator 72 is a calibrationinjection, as described above, and relative changes of sound velocityrelated to known blood flow Q_(dial) are measured by sensor 50. Therelative changes of sound velocity corresponding to injections made intoport 40 of indicator material 42 and into port 70 of the same indicatormaterial 72 are recorded by sensor 50, so that relative changes of soundvelocity in arterial line 26 due to these injections can be calculatedin detector 58 to obtain an accurate shunt blood flow measurement inaccordance with equation 5.

[0047] Still another embodiment of the invention is illustrated in FIG.5, which is similar to the embodiment of FIG. 2 but with the addition ofa sensor 80 located on the venous line, or tube, 32. Sensor 80 includesa sound transmitter 82 and a sound receiver 84, the receiver producingan output signal on output line 86 which is connected to detector 58.The use of sensor 80 avoids the need for additional calibrationinjections in arterial line 26. The additional sound velocity source 82and receiver 84 match the sound velocity source 52 and receiver 54, andsensor 80 is located downstream of the injection port 40 in venous line32. As a result, all of the indicator material 42 flows through sensor80, producing dilution curve 88 (FIG. 5A). The injection made in port 40is mixed only with the blood flow in venous line 32, and thus serves tocalibrate the sensor 80. The same injection later generates dilutioncurve 89 in the matching sensor 50 (FIG. 5B) after the indicatormaterial passes through the shunt vessel 12, and a portion isrecirculated into arterial line 26. The calculation of shunt blood flowQ_(shunt) is then made in accordance with Equation 8.

[0048] A second embodiment of the invention is illustrated in FIG. 6, towhich reference is now made. This embodiment provides a measurement ofundesired recirculation of freshly purified blood while utilizing a“normal” connection of the dialysis equipment lines. Thus, in thisembodiment the dialysis equipment 24 is connected to a patient'svascular system by way of shunt 12 and an arterial line 90 leading frominlet 92 to the dialysis equipment. Similarly, the equipment isconnected to shunt 12 by venous line 94 which delivers purified bloodfrom the dialysis equipment through outlet 96 in the shunt. Thedirection of blood flow in arterial line 90 is illustrated by arrow 98,and the direction of blood flow in venous line 94 is illustrated byarrow 100.

[0049] Although the outlet 96 is downstream from the inlet 92 in shunt12, nevertheless such a “normal” connection can produce undesiredrecirculation of purified blood, as illustrated by arrow 102. Thus,purified blood can flow upstream in vein 12 and be picked up at inlet 92for recirculation through the dialysis equipment, such recirculatedblood then making up a part of the arterial blood flow 98.

[0050] To measure this recirculation, an indicator material having aselected physical property differing from that of the blood is injectedinto the venous line 94 through an injection port 104. In the preferredembodiment, the indicator material, indicated by arrow 106, is a salinesolution isotonic with the blood, but having different sound velocityproperties. The injection of such an indicator dilutes the blood invenous line 94, and if recirculation exists, some of the diluted bloodwill appear in arterial line 90, producing resultant sound velocitychanges which will be recorded by a sensor 110 having a sound source 112and a sound receiver 114. The receiver 114 is connected by way of line116 to a detector 118 of the type described in the previous embodiment.The detector serves like as a measuring and evaluating device whichrecords the received signals which calculates the area under thedilution curve which results from the injection of the indicatormaterial, and which carries out the calculations prescribed by theequations described above.

[0051] An additional calibration injection of indicator material 120which is the same as the indicator material 106, may be injected by wayof a port 122 in arterial line 90, upstream of the sensor 110. Since allof the blood in the arterial line 90 will pass through the sensor 110,the indicator material injected at 122 will be mixed only with thisarterial blood flow, and the resulting dilution curve recorded bydetector 118 permits calibration of the system by calculating the areaunder the dilution curve and subsequent determination of therecirculation fraction in accordance with Equation 10. If it is desiredto avoid the need for a recalibration injection, a modified version ofthe device of FIG. 6 may be provided, as illustrated in FIG. 7. In thismodification, an additional sensor 130 having a sound velocity source132 and a sound velocity receiver 134 is provided on the venous line 94.The receiver 134 is connected by way of line 136 to the detector 118.The sensor 130 matches sensor 110 and is located downstream of theinjection port 104, so that all of the blood from the dialysis equipment24 as well as the indicator material 106 injected in port 104 will passthrough sensor 130. The sensor measures the dilution curve in thearterial blood 100, and the same injection then produces a dilution inthe flow 98 through arterial line 90. Sensor 110 detects the indicatormaterial to provide a resulting signal to detector 118 from which therecirculation can be calculated in accordance with Equation 11, asoutlined above with respect to the first embodiment and the variousmodifications thereof described with reference to FIGS. 1-5.

[0052] Although the present invention has been described in terms ofpreferred embodiments, it will be understood that variations andmodifications may be made without departing from the true spirit andscope thereof.

I claim:
 1. A process for determining in an arterio-venous shunt bloodflow in a cardiovascular circuit, comprising: (a) delivering blood froma circulating system outside the cardiovascular circuit into an upstreamlocation in an arterio-venous shunt connected in the cardiovascularcircuit and carrying a shunt blood flow; (b) combining the deliveredblood with the shunt blood flow; (c) removing a portion of the mixedblood from said arterio-venous shunt at a location in the shunt which isdownstream from said upstream location and delivering the removedportion of mixed blood to the circulating system; (d) altering aselected blood parameter in blood flowing in the circulating system toproduce a measurable physical characteristic of the blood which isdelivered to the arterio-venous shunt; (e) measuring the measurablephysical characteristic of the blood in the removed portion of mixedblood; and (d) determining the rate of flow of the shunt blood flow inthe arterio-venous shunt corresponding to the measured measurablephysical characteristic of the blood.
 2. The process of claim 1 ,further including measuring the rate of flow in the circulating system,and determining the arterio-venous shunt blood flow from the measuredmeasurable physical characteristic of the blood and the measured rate offlow.
 3. The process of claim 2 , wherein the step of altering aselected blood parameter includes changing a selected one of thethermal, optical and electrical impedance characteristics of bloodflowing in the circulating system.
 4. The process of claim 1 , whereinthe step of changing a selected blood parameter includes injecting anindicator material into blood flowing in said circulating system.
 5. Theprocess of claim 1 , wherein the step of changing a selected bloodparameter includes changing the velocity of sound in blood flowing insaid circulating system.
 6. The process of claim 1 , wherein the step ofchanging a selected blood parameter includes changing the electricalimpedance of blood flowing in said circulating system.
 7. The process ofclaim 1 , wherein the step of changing a selected blood parameterincludes changing the optical characteristics of blood flowing in saidcirculating system.
 8. The process of claim 1 , wherein the step ofchanging a selected blood parameter includes changing the thermalcharacteristics of blood flowing in said circulating system.
 9. Aprocess for determining patient blood flow in a patient hemodialysisshunt, comprising: removing blood from a downstream location in a hemodialysis shunt by way of an inlet connected to an inlet side of ahemodialysis circulating line to provide blood flowing in saidcirculating line; delivering the blood flowing in said circulating lineby way of an outlet connected to an outlet side of said circulating lineto an upstream location of said shunt, the blood from said outlet beingdelivered to said shunt so as to mix with patient blood flow in saidshunt to produce mixed blood, whereby blood removed from said shunt byway of said inlet is a portion of said mixed blood; changing a selectedblood parameter in said circulating line to produce a distinguishableblood characteristic at the outlet side of said circulating line;measuring in said circulating line the amount of said changed parameterpresent in said portion of the mixed blood; and determining the rate ofpatient blood flow in said shunt from the measured amount of saidchanged parameter.
 10. The process of claim 9 , further including:measuring the rate of flow in said circulating line to provide increasedaccuracy in determining patient blood flow rate in said shunt.
 11. Theprocess of claim 10 , wherein the step of changing a selected bloodparameter includes changing a selected one of the thermal, optical,electrical impedance and sound velocity characteristics of said bloodflowing in said circulating line.
 12. The process of claim 9 , furtherincluding: measuring in said circulating line the amount of said changedparameter, prior to delivering the blood from the circulating line tosaid upstream location to mix with said patient blood flow in saidshunt, to provide an increased accuracy in determining said patientblood flow rate.
 13. The process of claim 12 , further including:measuring blood flow rate in said circulating line to provide increasedaccuracy in determining blood flow rate in said shunt.
 14. The processof claim 12 , wherein measuring the amount of the changed parameter thatis present in said portion of mixed blood and wherein measuring theamount of the changed parameter that is present in said circulating lineprior to its mixing with the patient blood flow are performed at saidinlet side.
 15. The process of claim 14 , further including measuringblood flow rate in said circulating line to provide increased accuracyin determining blood flow rate in said shunt.
 16. The process of claim12 , wherein measuring the amount of said changed parameter present insaid portion of mixed blood takes place at said inlet side of saidcirculating line, and wherein measuring in said circulating line theamount of said changed parameter present in circulating line blood flowprior to delivering blood to said upstream location takes place at saidoutlet side of said circulating line.
 17. The process of claim 16 ,wherein measuring at said outlet side is carried out at a first locationin said circulating line and changing a selected blood parameter occursat a second location upstream from said first location.
 18. The processof claim 9 , further including: producing from the changed parametermeasurement an indicator dilution curve representing saiddistinguishable blood characteristic; and determining from saidindicator dilution curve said blood flow rate in said shunt.
 19. Theprocess of claim 9 , wherein measuring the amount of said changedparameter includes monitoring said portion of mixed blood at said inletside of said circulating line.
 20. The process of claim 9 , whereinchanging a selected blood parameter includes changing the velocity ofsound in said blood flowing in said circulating line.
 21. The process ofclaim 9 , wherein changing a selected blood parameter includes changingthe electrical impedance of said blood flowing in said circulating line.22. The process of claim 9 , wherein the step of changing a selectedblood parameter includes changing the optical characteristics of saidblood flowing in said circulating line.
 23. The process of claim 9 ,wherein changing a selected blood parameter includes changing thethermal characteristics of said blood flowing in said circulating line.24. Apparatus for determining line blood flow in a blood line of acardiovascular circuit, comprising: a blood circulating system includinga blood dialysis device outside the cardiovascular circuit; a blooddelivery line connectable between said circulating system and anupstream location in a cardiovascular circuit blood line to deliverblood from said circulating system to the blood line so as to mixdelivered blood with cardiovascular circuit line blood flow to produce ablood mixture; a blood intake line connectable between said circulatingsystem and a downstream location in the blood line to draw a portion ofsaid blood mixture into said circulating system; means for introducingan indicator into said blood delivery line; an indicator dilution sensorcoupled to said blood intake line to measure the concentration of saidindicator which is present in said portion of said blood mixture; andmeans for calculating, from said measure of concentration, the rate ofsaid line blood flow.
 25. The apparatus of claim 24 , further includinga blood flow indicator to record blood flow in said blood circulatingsystem.
 26. The apparatus of claim 24 , wherein the blood line is anarterio-venous shunt.
 27. The apparatus of claim 24 , wherein saidindicator sensor is an ultrasonic sensor.
 28. The apparatus of claim 24, wherein said indicator sensor is located in said intake line fordetecting the amount of said indicator in said portion of said bloodmixture.
 29. The apparatus of claim 28 , wherein said means forintroducing an indicator includes a first injection port located in saiddelivery line and a second injection port located in said intake linefor introducing a calibration indicator into said portion of said bloodmixture upstream of said intake line indicator sensor.
 30. The apparatusof claim 28 , further including a second indicator sensor on saiddelivery line downstream of said means for introducing an indicator fordetecting said indicator prior to the delivery of blood from saidcirculating system to the blood line.
 31. The apparatus of claim 30 ,wherein each said indicator sensor is an ultrasonic sensor. 32.Apparatus for determining shunt blood flow in a hemodialysis shuntconnected in a cardiovascular system comprising: indicator dilutionsensor means connected to a blood intake line in a hemodialysis bloodcirculating system adapted to deliver blood through a blood deliveryline to an upstream location in a shunt where delivered blood is mixedwith shunt blood flow, wherein the circulating system removes blood froma downstream location in the shunt by way of the intake line, andwherein the removed blood is a portion of the delivered blood mixed withblood flow in the shunt; recording means connected to said indicatordilution sensor means to register the amount of indicator in the removedblood resulting from introducing an indicator into the blood deliveryline; and calculator means connected to said recording means forcalculating the rate of flow of said shunt blood flow from said registerof the amount of indicator in the removed blood.
 33. The apparatus ofclaim 32 , further comprising blood flow indicator means connected tothe hemodialysis blood circulating system to record blood flow in saidsystem and connected to said calculator means to provide increasedaccuracy in the calculation of shunt blood flow rate.
 34. The apparatusof claim 33 , wherein said indicator dilution sensor means is one of athermal sensor, optical, electrical impedance and ultrasound sensor. 35.The apparatus of claim 32 , wherein said recording means furtherincludes means to register the amount of indicator resulting fromintroducing an indicator upstream from said sensor, to provide increasedaccuracy in the calculation of shunt blood flow rate.
 36. The apparatusof claim 35 , further comprising blood flow indicator means connected tothe hemodialysis blood circulating system to record blood flow in saidsystem and connected to said calculator means to provide increasedaccuracy in the calculation of shunt blood flow rate.
 37. The apparatusof claim 32 , further comprising second indicator dilution sensor meansconnected to the hemodialysis blood circulating system and connected tosaid recording means to record the amount of indicator in the bloodcirculating system prior to the delivery of blood to the shunt, toprovide increased accuracy in the calculation of shunt blood flow rate.38. The apparatus of claim 37 , further comprising blood flow indicatormeans connected to said hemodialysis blood circulating system to recordblood flow in said system and connected to said calculator means toprovide increased accuracy in the calculation of shunt blood flow rate.39. The apparatus of claim 37 , wherein said second indicator dilutionsensor means is one of a thermal sensor, optical, electrical impedanceand ultrasound sensor.
 40. The apparatus of claim 32 , wherein saidindicator dilution sensor means is an ultrasound sensor.
 41. Theapparatus of claim 32 , wherein said indicator dilution sensor is anoptical sensor.
 42. The apparatus of claim 32 , wherein said indicatordilution sensor means is an electrical impedance sensor.
 43. Theapparatus of claim 32 , wherein said indicator dilution sensor means isa thermal sensor.